We are utilizing the Chinese Hamster Ovary (CHO) fibroblast grown in vitro to study the genetics and biochemistry of some aspects of the behavior of cultured cells. Our work has emphasized morphology and its relationship to growth control, response to cyclic AMP, the role of cell surface antigens, receptors and internalization of their ligands in cell behavior, and the mechanism of cell transformation by tumor viruses. We have isolated a variety of different mutants with altered microtubules, abnormal morphology, or abnormal response to cyclic AMP and many of these have been characterized as to their biochemical defects. We have isolated cell mutants resistant to transformation by the product of the src gene of Rous sarcoma virus. We are establishing general procedures for the isolation of mutants unable to internalize specific ligands. These mutants are analyzed genetically using the techniques of somatic cell hybridization, gene cloning and gene transfer, and biochemically by classical enzymology, immunology, affinity labeling techniques and two-dimensional electrophoresis.